Carriers For Oral Delivery Research Articles

QbD-Steered Development of Biotin-Conjugated Nanostructured Lipid Carriers for Oral Delivery of Chrysin: Role of Surface Modification for Improving Biopharmaceutical Performance

Bioactives are documented to exhibit diverse pharmacological activities, however, their low and inconsistent bioavailability primarily pose serious impediment against their potential therapeutic usage. Efforts, therefore, have been undertaken to systematically develop nanostructured lipidic carriers of chrysin, a vital flavonoid, employing Capmul PG-12 (i.e., liquid lipid), glyceryl monostearate (i.e., solid lipid), stearylamine, Phospholipid S-100 (i.e., cosurfactant) and Poloxamer 188 (i.e., surfactant). NLCs were formulated using hot-melt dispersion-high pressure homogenization method and optimized using Face-Centred Cubic Design. Afterwards, stearylamine was conjugated with biotin as ligand through EDC-NHS coupling reaction and biotin-staerylamine complex formation was ratified using H-1NMR and FTIR. It was further used instead of SA for the preparation of biotin-conjugated-optimized NLCs (Bio-NLCs). Mean particle size of consequent Bio-NLCs was found to be 246.4 nm and zeta potential as 11.4 mV. In vitro release studies indicated sustained drug release characteristics from NLCs over 48 h. Cell line studies conducted on coumarin6-loaded Bio-NLCs in demonstrated remarkably superior cellular uptake over naive NLCs and pure dye. Marked improvement in absorption parameters was observed during in vivo pharmacokinetics for Bio-NLCs and NLCs vis-à-vis pure chrysin suspension. However, the improvement for naive NLCs was relatively lower than that of Bio-NLCs. Almost 5.20-folds augmentation in Cmax (p < 0.005), 8.94-folds in AUC0-24 (p < 0.001), 7.46-folds in AUC0-∞ (p < 0.001) and 7.25-folds in Ka (p < 0.01), signify improved degree of drug absorption and retention of Bio-NLCs. Stability studies indicated the robustness of Bio-NLCs, when stored under refrigerated storage conditions for 3 months. By and large, the current work demonstrates high potential of Bio-NLCs for distinctly improved biopharmaceutical performance of chrysin.

Formulation and In Vitro Characterization of Raloxifene Nanostructured Lipid Carriers For Oral Delivery With Full Factorial Design-Based Studies Using Quality By Design (QbD) Approach

The main aim of the present study is to improve the dissolution rate of Raloxifene Hydrochloride by formulating nanostructured lipid carriers (NLC) using Quality by Design (QbD) approach. The formulations of NLC-RH were prepared by the ultrasonication method using stearic acid as solid lipid, medium-chain triglyceride as the liquid lipid and polysorbate 80 as the surface-active agent. Two most critical quality attributes (CQAs) for NLC-RH were particle size and entrapment efficiency. The other attributes of medium influence identified includes dissolution rate, zeta potential and particle size didtribution. The Critical Material Attributes (CMAs) identified were solid lipid/liquid lipid ratio and surfactant concentration. The time required for ultrasonication was selected as a Critical Process Parameter (CPP). The 23 full factorial design was used to evaluate the relationship between the CMAs and CPPs variable. Based on the experiments, the composition of the optimal formulation is achieved with solid lipid/liquid lipid ratio of 7:3 and 7 % of surfactant concentration with 15 min of ultrasonication time. The optimized formulation of NLC-RH was found to be with a mean particle size of 146 nm with narrow particle size distributions. From the above results, it is concluded that a promising Raloxifene HCl loaded NLC could give a novel and potential therapy for osteoporosis.

Inclusion complex based on N-acetyl-L-cysteine and arginine modified hydroxypropyl-β-cyclodextrin for oral insulin delivery

Insulin is the most effective drug in the treatment of diabetes mellitus. At present, subcutaneous injection is still the common way for insulin delivery. However, oral delivery is considered as the most preferred way for its high patient compliance and the minimal invasiveness. In this study, a novel N-acetyl-L-cysteine and arginine modified hydroxypropyl-β-cyclodextrin (NAC-HP-β-CD-Arg) was successfully synthesized and characterized. The polymer was used as a carrier for oral delivery of insulin by forming NAC-HP-β-CD-Arg@insulin complex. Enzymatic degradation study indicated that the NAC-HP-β-CD-Arg could protect insulin from enzymolysis. Moreover, the polymer exhibited strong binding ability with mucin. The transportation efficiency of NAC-HP-β-CD-Arg@insulin across the Caco-2 cell monolayer was much greater than free insulin. The in vivo study demonstrated that the orally administered NAC-HP-β-CD-Arg@insulin exhibited an excellent and sustained hypoglycemic effect in diabetic rats. It can be concluded that the NAC-HP-β-CD-Arg is a potential carrier for oral delivery of insulin.

Nanostructured Lipid Carriers- A Versatile Carrier for Oral Delivery of Lipophilic Drugs.

Around 40% of newly discovered chemical entities in pharmaceutical industries have poor water solubility and hence they suffer from low oral bioavailability owing to undesirable physicochemical and pharmacokinetic properties. So, it is the challenge for the formulation scientists to develop the oral formulation that can mitigate the pitfalls associated with such lipophilic drugs. Lipid nanoparticles hold a promising tool to decrease the pitfalls of lipophilic drugs as lipid components can effectively increase the absorption of drugs, which leads to improvement in oral bioavailability. They are also considered as safe because they are made up of physiological lipids, which are biocompatible and biodegradable in nature. Amongst the lipid nanoparticles, Nanostructured Lipid Carriers (NLCs) are the second-generation lipid nanoparticles and were developed to conquer the limitations of solid lipid nanoparticles. They increase the solubility, permeability, reduce metabolism, P-glycoprotein efflux, and thereby increase the bioavailability of poorly soluble drugs. This review highlights the various aspects of NLCs, such as structural components, types, in vivo fate, pharmacokinetic, toxicity, recent applications, and patent reviews of NLCs in drug delivery.

Green one-pot synthesis of multicomponent-crosslinked carboxymethyl cellulose as a safe carrier for the gentamicin oral delivery

Multicomponent reactions (MCRs) as a green strategy was used to crosslink carboxymethylcellulose (CMC) via the construction of bioactive carboxamide skeletons for the gentamicin (GM) oral delivery. The prepared multicomponent-crosslinked (MCC) CMC hydrogels (CMC-MCC) were fully characterized using various methods. To explain the productivity of the prepared system, GM delivery tests performed in the simulated gastrointestinal tract (GIT) conditions. CMC-MCC could efficiently protect the loaded-GM against the acidic environment of the stomach and enhance the sustainability of drug dosing with controlling the releases in the GIT circumstances. The antibacterial performance showed that the GM-loaded CMC-MCC has notable activity against S. aureus and E. coli bacteria. Besides, the cytotoxicity study indicated that CMC-MCC toward healthy normal human umbilical vein endothelial cells (HUVEC) has a cytocompatibility nature.

Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: role of P-gp inhibition.

Linagliptin (LGP), a novel anti-diabetic drug, is a DPP-4 inhibitor used in the treatment of type II diabetes. One of the major disadvantages of LGP is its low oral bioavailability (29.5%) due to first-pass metabolism and P-gp efflux. In an attempt to increase the oral bioavailability, LGP solid lipid nanoparticles (LGP-SLNs) were developed with poloxamer 188 and Tween 80 as P-gp inhibitors. LGP-SLNs were formulated using palmitic acid, poloxamer 188 and Tween 80 as lipid, surfactant and co-surfactant, respectively, by hot homogenization ultrasonication method and optimized using 32 full factorial designs. Particle size, entrapment efficiency (%EE) and drug release at 24h were evaluated as responses. An optimized batch of LGP-SLNs (L12) was evaluated for intestinal transport of LGP by conducting in situ single-pass intestinal perfusion (SPIP), everted gut sac and Caco-2 permeability study. The pharmacokinetic and pharmacodynamic evaluation of L12 was carried out in albino Wistar rats. The mean particle size, polydispersity index, zeta potential and %EE of L12 were found to be 225.96 ± 2.8nm, 0.180 ± 0.034, - 5.4 ± 1.07mV and 73.8 ± 1.73%, respectively. %CDR of 80.96 ± 3.13% was observed in 24h. The permeability values of LGP-SLNs in the absorptive direction were 1.82-, 1.76- and 1.74-folds higher than LGP-solution (LGP-SOL) in SPIP, everted gut sac and Caco-2 permeability studies, respectively. LGP-SLNs exhibited relative bioavailability of 300% and better reduction in glucose levels in comparison with LGP-SOL in rats. The enhanced oral bioavailability exhibited by LGP-SLNs bioavailability may be due to P-gp efflux inhibition and lymphatic targeting. Improved bioabsorption can cause reduction in dose, dose-related side effects and frequency of administration. Thus, LGP-SLNs can be considered promising carriers for oral delivery but clinical studies are required to confirm the proof of concept.Graphical abstract.

β-Cyclodextrin-based (IA-co-AMPS) Semi-IPNs as smart biomaterials for oral delivery of hydrophilic drugs: Synthesis, characterization, in-Vitro and in-Vivo evaluation

Currently, the synthesis of multi-polymer based hydrogels called interpenetrating networks (IPNs) is more in practice due to enhanced tunability and effective drug release features in comparison to single components. IPNs are synthesized by crosslinking two or more polymeric networks where one of the networks is synthesized in the presence of the other network. In comparison to conventional hydrogels, the IPN systems exhibit enhanced mechanical features with good swelling, drug entrapment and release profile. The objective of this study was to prepare β-CD-based pH-responsive semi-IPN hydrogels utilizing the strong ionizable functionalities of itaconic acid (IA) and 2 acrylamido-2methylpropane sulfonic acids AMPS. The semi-IPNs were prepared through free radical polymerization technique using N, N′-methylene bisacrylamide (MBA) as a crosslinking agent and ammonium persulfate (APS) as reaction imitator. Loxoprofen sodium was chosen as a model drug. The network formation and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR) while thermal behavior was evaluated through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to check the change in the crystallinity and morphology of the prepared semi-IPNs. The behavior, efficiency, safety and oral tolerability of the semi-IPNs were tested through various in-vitro and in-vivo studies. FTIR results confirmed the successful crosslinking and drug loading in the semi-IPNs while TGA and DSC proved their thermal stability. XRD showed a decrease in crystallinity while SEM confirmed the uneven and rough surface with some cracks. The semi-IPNs exhibited high swelling and drug release at pH 5.5 and 7.4 than the acidic pH 1.2. Drug release followed first-order kinetic while release phenomena was diffusion-based following non-Fickian mechanism. Oral tolerability suggested that the hydrogel dispersion was well tolerable up to 3200 mg/kg without causing any histopathological or hematological changes. The obtained results suggested that β-CD-IA-AMPS semi-IPNs could be a safe and efficient carrier for oral delivery of hydrophilic drugs.

Characterization of Bovine Lactoferrin Nanoparticle Prepared by Desolvation Technique.

Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100-200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.

In Vitro Evaluation of a Fluorescent Microemulsion as an Oral Delivery Carrier and its Potential Application in Tracking Bioactive Compounds Label-Free.

In this work, a microemulsion emitting fluorescence was fabricated as a potential oral delivery system for bioactive compounds. In simulated oral administration, the microemulsion was characterized for its microstructure by 1hydrogen-nuclear magnetic resonance (1H-NMR). Results showed that microemulsions not only have good resistance to oral and gastric phases, but also lay a solid foundation for the release of bioactive compounds in the intestine. Fluorescence stability tests showed that microemulsions exhibit a remarkable fluorescence intensity in the digestive environment, indicating feasibility as a label-free delivery carrier. Moreover, in vitro release tests of bioactive compounds confirmed that an α-linolenic acid (ALA)-loaded microemulsion mainly released in the intestine, thereby achieving the aim of controlling the release of bioactive compounds. These results suggest that the synthesized fluorescent microemulsion, combining the favorable features of nontoxicity, antidigestive stability, remarkable fluorescence intensity, and controllable release, can be regarded as a promising label-free delivery carrier for oral administration.

Impact of liquid lipid on development and stability of trimyristin nanostructured lipid carriers for oral delivery of resveratrol

Nanostructured lipid carriers (NLCs) have emerged as versatile carriers to improve oral bioavailability of poorly water-soluble drugs as well as to protect labile drugs from degradation and metabolism. Prepared by blending solid and liquid lipids, the choice of liquid lipid can have a great influence on their physicochemical characteristics and stability. The present work investigated the impact of six different liquid lipids with diverse chemical structures and hydrophilic and lipophilic balance (HLBs) on the critical quality attributes (CQAs) and storage stability of NLCs with trimyristin as solid lipid. Resveratrol (RES) was used as model drug as its low water solubility, poor bioavailability, rapid metabolism and clearance from systemic circulation restricts its clinical use despite its wide spectrum of biological activities. Liquid lipids investigated included, two triglycerides, one medium chain (C8) glycerol tricaprylate (GTC) and second, long chain (C18) glyceryl trioleate (GTO); two propylene glycol fatty acid esters, propylene glycol monocaprylate (PGMC) and propylene glycol monolaurate (PGML); fatty acid ester decyl oleate (DO) and a PEGylated lipid polyethylene glycol-8 caprylic/capric glycerides (PCG). Box–Behnken experimental design was employed to ascertain the effect of four independent factors viz. type of liquid lipid, amount of liquid lipid, amount of drug and surfactant concentration and interactions between these factors on the CQAs of NLCs as response variables viz. particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (DL). The relationship between various factors and responses was established by response surface methodology (RSM). The oils with higher lipophilicity C18 triglycerides (GTO) and C18 fatty acid ester DO yielded NLCs with lower PS as compared to the oils with lower lipophilicity (PGC, PGMC and PGML). Although increasing the concentration of liquid lipids had an upward trend on the PS of NLCs, its PDI was more predominantly influenced by the nature of liquid lipid. The characteristic of the liquid lipid influenced the DL remarkably which varied from 2.94 to 7.56%. The ZP of nanoparticles varied from −21.3 to −39.9 mV with liquid lipids with free hydroxyl groups and higher HLB playing a more prominent role contributing to the increase in the negative surface charge. The characteristics of liquid lipid influenced the depression of melting point of RES with maximum distortion of the crystal lattice was caused by PGMC and least by GTO. The two, long chain oleates, DO and GTO exhibited a shift of lipid peak in NLCs to higher melting points (116 and 111 °C) than the less lipophilic liquid lipids (103–104 °C). The attributes of liquid lipid also discriminate whether the particle growth during storage followed Oswald's ripening or coalescence. NLC containing GTO exhibited the highest stability in terms of maintenance of the PS and particle size distribution at 20 °C. This study provides vital insight on impact of liquid lipids and future strategy for rational design of stable NLC systems for delivery of various bio-actives for drug delivery applications.

Casein nanoparticles as oral delivery carriers of mequindox for the improved bioavailability

Mequindox (Meq) is a promising broad-spectrum antibacterial agent, but the clinical application of Meq has been hampered by its low oral bioavailability. Casein (Cas) can bind to a variety of poorly water-soluble drugs to improve their water solubility through a micellar solubilization mechanism. Here, a low-cost and convenient method was introduced to prepare mequindox-loaded casein nanoparticles (Meq-Cas). Meq-Cas was characterized by several methods including differential scanning calorimetry (DSC), X-ray diffraction (XRD), and fourier transform infrared (FTIR) to illuminate the mutual effect between the drug and carriers. Meq-Cas presented nearly spherical nanoparticles with smooth surfaces and its mean particle size was lower than untreated Cas. Meq-Cas showed a nearly complete release of Meq, which displayed a biphasic drug release pattern in both phosphate-buffered solution (PBS) and simulated gastric fluid (SGF). The relative oral bioavailability of Meq-Cas was found to be about 1.20 times higher than that of the animals treated with Meq suspension (control). These results suggest that Cas is a good candidate to load in Meq for pharmaceutical purposes.

Prediction of the enhanced insulin absorption across a triple co-cultured intestinal model using mucus penetrating PLGA nanoparticles.

Insulin is a protein macromolecule used to treat diabetes mellitus. Currently, insulin requires multiple daily subcutaneous (SC) injections to control blood sugar in diabetics. Thus, reducing the patients' compliance and adherence to medication as SC route is invasive. Insulin is poorly absorbed through intestinal epithelium because it is a large and hydrophilic molecule, degraded by proteases, and due to the presence of mucosal biophysical barrier. Herein, insulin was encapsulated into different poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) formulations prepared by microfluidic technique, which were further appended with heparin sulfate for oral insulin delivery. The average particle size was ca. 200nm, PDI at ca. 0.3 and the zeta potential at ca. -20mV. The maximal achieved association efficiency of insulin was~55% at 3% theoretical loading. PLGA exhibited a protective effect against insulin release in harsh acidic conditions (pH=2.2) with only a small burst release (~15%) and sustained release at pH 6.8. Although the encapsulation process altered insulin secondary structure whilst encapsulated into PLGA NPs, insulin restored its tertiary structure once released from the NPs. Mucopenetrating heparin sulfate conjugated PLGA NPs significantly improved insulin permeability in triple co-cultured intestinal model compared to unmodified and free insulin with two and three-fold increase. Thus, they could be utilised as carriers for oral insulin delivery.

Delivery of polysaccharides from Ophiopogon japonicus (OJPs) using OJPs/chitosan/whey protein co-assembled nanoparticles to treat defective intestinal epithelial tight junction barrier

The polysaccharides from Ophiopogon japonicus (OJPs) were known to have protective effects against diabetes, and cardiovascular and chronic inflammatory diseases. However, OJPs were poorly absorbed after oral administration, resulting in limited efficacy because of the low bioavailability. In this study, OJPs extracted and fractionated from Ophiopogon japonicus were used to prepare OJPs/chitosan (CS)/whey protein (WP) co-assembled nanoparticles. The OJPs/CS/WP nanoparticles showed high biocompatibility and inhibited the cytotoxicity of RAW264.7 cells induced by nickel. With the assistance of CS and WP, the anti-inflammatory and antioxidant activities of OJPs were enhanced because the nanoparticles improved OJPs uptake by RAW264.7 macrophage cells as evidenced by efficient scavenging of DPPH and ABTS free radicals and effective inhibition of NO production and the gene expressions of iNOS, COX2, TNF-α, CCL2, and CXCL2 inflammatory signals. Determining the transepithelial electrical resistance and paracellular permeability of Caco-2 monolayer/macrophage co-cultured system suggested that the OJPs-loaded nanoparticles effectively protected the intestinal epithelial barrier integrity against the damage caused by LPS-stimulated macrophage inflammation and attenuated the defects of intestinal epithelial TJ barrier and permeability. These findings suggest that the OJPs/CS/WP nanoparticles may be potential carriers for oral delivery of OJPs to treat intestinal barrier defects, such as inflammatory bowel disease (IBD).

Ionic gelated β-cyclodextrin-biotin-carboxymethyl chitosan nanoparticles prepared as carrier for oral delivery of protein drugs

Abstract In this paper, the β-cyclodextrin (β-CD) and biotin (Bi) were successfully grafted onto carboxymethyl chitosan (CMCS). And then the β-CD-Bi-CMCS nanoparticles (NPs) were prepared as oral nano-delivery carrier of protein drugs by ionic gelation method. The morphological feature of fabricated drug carrier was determined by dynamic light scattering and transmission electron microscopy. The result showed that the prepared NPs presented spherical structure with an average diameter of 138 nm. Bovine serum albumin (BSA) was selected as model protein drug that was entrapped in prepared drug carrier with satisfactory entrapment efficiency (79.18%) and loading content (3.96%). The drug release profiles of BSA/β-CD-Bi-CMCS NPs were studied at different pH environment for simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). It was found that the BSA/β-CD-Bi-CMCS NPs displayed a pH dependent drug release profiles. After 72 h, the cumulative release amount of BSA in SGF, SIF, and SCF was about 20.57, 74.46, and 91%, respectively. Furthermore, the enzymatic degradation and cytotoxicity studies showed the synthesized β-CD-Bi-CMCS NPs had high chemical stability and biocompatibility. This work indicated that the β-CD-Bi-CMCS NPs had the potentiality as promising nanocarriers for oral delivery of protein drugs.

Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation

Crossing the intestinal mucus layer remains a great hurdle in oral drug delivery. The viscous mucus gel protects the body from pathogens but simultaneously traps many types of delivery vehicles, limiting their therapeutic efficacy. We report the assembly of mucopenetrating PEG-based polymer-lipid hybrid vesicles encapsulated in mucoadhesive alginate carriers aiming to increase their residence time in the intestine. The stability of the formulations was evaluated in simulated gastrointestinal conditions, showing negligible subunit leakage in the gastric fluid but a substantial release in the intestinal fluid. Mucopenetration of the free and encapsulated subunits was first demonstrated in vitro in a microfluidic set-up filled with reconstituted porcine mucus and in a mucus-covered co-culture of Caco-2 cells and HT29-MTX-E12 cells. Finally, the free and encapsulated subunits remained adhered in close proximity to the intestinal epithelium after oral administration to rats while the alginate carriers were washed away. In conclusion, the double-encapsulated system with combined mucoadhesive and mucopenetrating properties is a promising alternative drug carrier for oral delivery.

COMPUTATIONAL DESIGN OF NOVEL ORAL INSULIN CONJUGATES FOR THE DEVELOPMENT OF SOLID ORAL INSULIN DOSAGE FORMS

Objective: Insulin is used to manage diabetes mellitus by subcutaneous injections regulary, that has become a part of patients life and is distressing for patients. Hence, we anticipate to get rid of the usage of subcutaneous injections completely from the medicine world and would make the diabetic people to say as “farewell to painful injections.”&#x0D; Methods: Virtual screening method (for selection of carriers), Toxtree tool (for toxicity evaluation of carriers), and discovery studio tool (for pharmacophore designing, absorption, distribution, metabolism, excretion, and toxicity [ADMET] analysis, designing oral insulin conjugates (OICs), and interaction studies between insulin receptor and OICs) were used for proposed study.&#x0D; Results: We have screened 14 competent drug delivering molecules (DDMs) from seven chemical compound databases. The ADMET and pharmacophoric properties of DDMs were analyzed by drug-informatics’ tools. Consequently, the DDMs were mono, di, and poly conjugated by covalent bonding with various binding sites of monomeric and hexameric form of human insulin and insulin-lispro (Humalog®) individually; and novel OICs were generated. Its binding efficiency and biological activity with insulin-receptor were determined.&#x0D; Conclusion: Inulin and Vitamin-B1 are the novel, safe, and proficient carriers for oral delivery of insulin. Insulin lispro is the remarkable option for oral delivery than other insulin forms.

Design and characterization of chitosan/citrate films as carrier for oral macromolecule delivery

The oral delivery of biopharmaceuticals requires the including of absorption enhancer, protease inhibitor and a suitable carrier system. The aim of the present work was to formulate and characterize chitosan solutions/films incorporating citric acid (CA) as potential excipient in comparison to the well-known acetic acid (AA)-based films as a reference. Films were made by the solvent casting method with/without glycerol (G), propylene glycol (PG) and polyethylene glycol (PEG-400) as plasticizers. The minimum film forming temperature (MFFT) of the prepared solutions, film thickness, hardness/deformation, mucoadhesivity, moisture content, FT-IR spectra and surface free energy (SFE) were investigated. Chitosan has been reported as a safe and effective paracellular absorption enhancer for hydrophilic macromolecules, therefore there would be more rationale for incorporating CA as a solubility enhancer, a permeation enhancer and an enzyme inhibitor. CA shows good cross-linking, an ideal plasticizing property and increases both tensile strength and mucoadhesivity, thus its incorporation simplifies the formulation while improving effectiveness. We concluded that CA (3.5, 4 and 5 w/v %)-based chitosan solution could be used as a novel coating/subcoating polymer for oral macromolecule delivery, or as oral mucoadhesive films.

Polymeric Microparticles as Alternative Carriers for Antidiabetic Glibenclamide Drug

Background: Glibenclamide is a lipophilic drug widely used in type 2 diabetes treatment. However, its low bioavailability limits its use. Thus, novel formulations should be applied to improve the drug’s bioavailability.&#x0D; Objectives: This study aimed to develop alternative carriers for oral delivery of glibenclamide. For this purpose, two biocompatible polymers, poly(e-caprolactone) and poly(butylene adipate) were formulated as microparticles (MPs) capable of loading the antidiabetic drug.&#x0D; Methods: In this regard, as microparticle fabrication approach, the modified emulsion solvent evaporation method was applied. Physicochemical evaluation of the prepared microparticles included the examination of their morphology, degradation rate, and thermal properties. Drug entrapment, drug loading, and particle size were also investigated. Simulated intestinal medium and body fluid at 37oC were selected as dissolution media. Differential scanning calorimetry was used to investigate the crystal properties of the microparticles and drugs.&#x0D; Results: The developed microparticles had sizes between 0.5 and 4 μm. Poly(butylene adipate) based microparticles had a smooth surface, whereas poly(ε-caprolactone) based microparticles showed a porous surface. The DSC thermogram revealed the amorphization of the drug. Hydrolysis results exhibited a very low mass loss, while in vitro release results depicted that the dissolution rate of the prepared microparticles was higher than that of pure glibenclamide demonstrating a prolonged pattern which is ideal for minimizing the daily dose of glibenclamide.&#x0D; Conclusion: In this study, novel carriers for glibenclamide were successfully prepared with promising future use.

Synthesis of Tilmicosin Nanostructured Lipid Carriers for Improved Oral Delivery in Broilers: Physiochemical Characterization and Cellular Permeation.

This study aimed to develop nanostructured lipid carriers (NLCs) for improved oral absorption of tilmicosin (TMS) in broilers. Thus, palmitic acid, lauric acid, and stearic acid were selected as solid lipids to formulate TMS-pNLCs, TMS-lNLCs, and TMS-sNLCs, respectively. They showed similar physicochemical properties and meanwhile possessed excellent storage and gastrointestinal stability. The TMS interacted with the lipid matrix and was encapsulated efficiently in NLCs in an amorphous structure. NLCs could enhance oral absorption of TMS compared to 10% tilmicosin phosphate solution in broilers, among which the TMS-sNLCs were the most efficient drug delivery carriers, with a relative oral bioavailability of 203.55%. NLCs could inhibit the efflux of P-glycoprotein (P-pg) toward TMS, which may be involved with improved oral absorption. Taken together, these types of solid lipids influenced the enhanced level of NLCs toward oral bioavailability of TMS, and the sNLCs proved to be the most promising oral delivery carriers of TMS.

Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis

The study investigated chitosan coated nanostructured lipid carriers (NLCs) for oral delivery of albendazole in treatment of trichinellosis. NLCs comprised precirol and oleic acid with Tween and Span 80. Dicetylphosphate was used as charging agent to allow chitosan coating. Trichinella spiralis infected mice were used and albendazole suspension, coated or uncoated NLCs were orally administered at different stages of infection. NLCs were spherical with size of 188 and 200 nm for coated and uncoated NLC, respectively. Treatment during intestinal phase reduced worm count with NLCs showing better rank. This was reflected further by reduced larvae count and improved histopathological features. Starting treatment in the migrating phase reduced larval count by 62.9, 99.6 and 89.5 % after administration of suspension, coated and uncoated NLCs, respectively. The same rank was recorded for the encysted phase. NLCs enhanced the efficacy of albendazole against Trichinella spiralis compared with suspension with chitosan coated NLCs being superior.